Результаты поиска

Identification of fidelity-determined residues of Porcine reproductive and respiratory syndrome virus through structural alignment.

Porcine reproductive and respiratory syndrome virus(PRRSV) is an economically important pathogen for global pork industry. As a positive-str … GS), it was found that the nsp9 K541R mutation enhances fidelity, as increasing viral resistance to mutagens like ribavirin, 5-Fluorouracil(5-FU), and 5-Azacytidine(5-AZC), as well as generating lower rate of non-contiguous junctions. In contrast, mutations at other positions, including A394G, L396S, and R401A, reduced fidelity and elevated frequency of re …

Comprehensive detection of unintentional hazardous substances in e-cigarette liquids.

INTRODUCTION: E-liquids can be unintentionally contaminated with various harmful substances, and the nicotine and glycols they contain can u … , and 2B) by the International Agency for Research on Cancer, and 8 were classified as carcinogens, mutagens, and reproductive toxicants by the European Union. The 25 organic solvents detected are regulated by the United States Pharmacopeia. Ethylene glycol exceeded the residual solvent limit by up to 368-fold in 71 brands, ethanol by up to 26-fold in 3 br …

Distinct mutational landscapes for germline and somatic cancer variants in forty tumor suppressor genes.

Germline and somatic cancer variants in tumor suppressor genes (TSGs) share loss-of-function mechanisms, but studies of a few genes (DICER1 … quence. Analysis by tumor type revealed excess stop-gain events in tissues exposed to environmental mutagens with corresponding mutation signatures. For several TSGs (WT1), germline variants predispose to tumors (Wilms' tumor) distinct from the majority source of somatic data (myeloid leukemia). Germline and somatic events are also distributed unevenly acr …

Suppressed DNA repair capacity in flight attendants after air travel.

Elevated cancer risk and compromised reproductive health have been well documented in flight attendants (FA), but the etiology remains unknown. Many studies using cell and animal models suggest that air travel related exposures might plausibly explain the adverse health outcomes observed in flight crew, but our understanding of the underlying biological mechanisms is incomplete. During air travel, FA are constantly exposed to complex mixtures of mutagens in the flight cabin that may contribute to genomic instability by inducing DNA damage and interfering with DNA repair. Defects in DNA repair …

Natural alkaloids targeting EGFR in non-small cell lung cancer: Molecular docking and ADMET predictions.

The phytochemicals contribute to the processes of protection and interaction by acting as antioxidants, anti-mutagens, anticarcinogens, and antimicrobial agents. Among the diverse families of phytoconstituents, alkaloids play an essential role in medicine. These are low-molecular-mass compounds containing nitrogen and are generally alkaline. In this study, in silico molecular docking was performed using AutoDock Vina for thirty-one alkaloids against epidermal growth factor receptor (EGFR). Erlotinib was used as a reference ligand for this study. Erlotinib has been linked to various serious sid…

Низкая верность венесуэльского энцефалита вируса полимеразы мутантов для повышения безопасности и эффективности вакцин.

Во время репродукции вируса RNA существует возможность инкорпорировать мутации, которые влияют на вирулентность или патогенез. Для живых вакцин это имеет последствия для стабильности, поскольку репликация может привести к мутации, которая либо восстановит фенотип дикой природы посредством реверсии, либо компенсирует смягчающие мутации путем увеличения вирулентности (pseudoreversion). Недавние исследования показали, что изменение скорости мутации вируса РНК является эффективным средством смягчения последствий. Для подтверждения безопасности низкодостоверных мутации в целях повышения степени сгл

Совпадение в аннотации оригинала
During RNA virus replication, there is the potential to incorporate mutations that affect virulence or pathogenesis. For live-attenuated vac … cephalitis virus vaccine strain, TC-83. Next generation sequencing after passage in the presence of mutagens revealed a mutant containing three mutations in the RdRp, TC-83 3x, to have decreased replication fidelity, while a second mutant, TC-83 4x displayed no change in fidelity, but shared many phenotypic characteristics with TC-83 3x. Both mutants exhib …

Assessment of antimutagenic action of Celtis glabrata Steven ex Planch. (Cannabaceae) extracts against base pair exchange and frame shift mutations on Salmonella typhimurium TA98 and TA100 strains by Ames test.

CONTEXT: Celtis glabrata is used in Turkey for the treatment of various health disorders. OBJECTIVE: The acetone, chloroform, ethanol, and methanol extracts of C. glabrata leaf, fruit, and seed were investigated to evaluate their antimutagenic activities. MATERIAL AND METHODS: The antimutagenicity of these extracts was determined by Ames test against mutagens (4-nitro-O-phenylenediamine, 2-aminofluorene (2-AF), and sodium azide (SA)). The extracts were used at concentrations between 5 and 0.005 mg/plate. RESULTS: The ethanol extracts of leaves exhibited strong antimutagenicity (70%) against…

Human alveolar epithelial cell injury induced by cigarette smoke.

BACKGROUND: Cigarette smoke (CS) is a highly complex mixture and many of its components are known carcinogens, mutagens, and other toxic substances. CS induces oxidative stress and cell death, and this cell toxicity plays a key role in the pathogenesis of several pulmonary diseases. METHODOLOGY/PRINCIPAL FINDINGS: We studied the effect of cigarette smoke extract (CSE) in human alveolar epithelial type I-like (ATI-like) cells. These are isolated type II cells that are differentiating toward the type I cell phenotype in vitro and have lost many type II cell markers and express type I cell marke…

High susceptibility of neonatal mice to molecular, biochemical and cytogenetic alterations induced by environmental cigarette smoke and light.

Our recent studies have shown that both cigarette smoke and UV-containing light, which are the most widespread and ubiquitous mutagens and carcinogens in the world, cause systemic genotoxic damage in hairless mice. Further studies were designed with the aim of evaluating the induction of genotoxic and carcinogenic effects in Swiss albino mice exposed to smoke and/or light since birth. We observed that a 4-month whole-body exposure of mice to mainstream cigarette smoke, starting at birth, caused an early and potent carcinogenic response in the lung and other organs. Our further experiments show…

Ectopic expression of tyrosinase increases melanin synthesis and cell death following UVB irradiation in fibroblasts from familial atypical multiple mole and melanoma (FAMMM) patients.

Patients with familial atypical multiple mole and melanoma (FAMMM) [so-called familial dysplastic naevus syndrome (FDNS)] have a high risk for the development of malignant melanoma. The underlying gene defect has an autosomal dominant inheritance with variable expression and incomplete penetrance. Fibroblasts derived from FAMMM patients have high sensitivity to UVC and mutagens, e.g. 4-nitroquinoline-1-oxide. We were interested in identifying how the combination of inherent sensitivity to UV light and abnormal melanin synthesis interacts in the development of melanoma in FAMMM patients. Interm…

Mutation and abnormal expression of the p53 gene in the viral skin carcinogenesis of epidermodysplasia verruciformis.

Patients suffering from epidermodysplasia verruciformis are prone to nonmelanoma skin cancers, due to an inherited abnormal susceptibility t … induced p53 mutations, as in nonmelanoma skin cancers in the general population, or involving other mutagens or mechanisms. The part played by human papillomavirus type 5 proteins expressed in epidermodysplasia verruciformis keratinocytes remains to be determined.

Protective effects of extracted human-liver RNA, a known interferon inducer, against radiation-induced cytogenetic damage in male mice.

Cells in vitro or in vivo pre-exposed to low-dose radiation (LDR) or low concentrations of chemical mutagens became more resistant to large-dose radiation-induced DNA or chromosome damage. This was known as radio-adaptive response, for which the exact mechanism was unclear. However, multiple cellular and molecular responses to LDR have been documented, for instance, the induction of some cytokines such as interferon (IFN). Administration of exogenous IFN to cultured cells or mice showed marked radio-protection. In the present study, we investigated the in vivo radio-protective effects of extra…

Acrylamide-induced chromosomal damage in male mouse germ cells detected by cytogenetic analysis of one-cell zygotes.

Within a project coordinated by the Commission of the European Communities for the detection of germ cell mutagens, the cytogenetic analysis of first-cleavage metaphases was carried out to detect chromosomal damage induced by acrylamide (AA) in meiotic and postmeiotic stages of mouse spermatogenesis. Male mice were intraperitoneally injected with single acute doses of 75 or 125 mg/kg or treated with five daily injections of 50 mg/kg and mated either 7 or 28 days after the end of treatment. Chromosomal aberrations were scored in C-banded metaphases prepared from one-cell zygotes by a mass harve…

Biomonitoring of the Paraopeba river: Cytotoxic, genotoxic and metal concentration analysis three years after the Brumadinho dam rupture - Minas Gerais, Brazil.

The rupture of Vale S.A. mining tailings dam in Brumadinho, Brazil, in January 2019 had significant environmental impacts on the Paraopeba River basin. Additionally, severe floods in early 2022 contributed to the transport of particles in the river. This study aimed to evaluate the cytotoxic and genotoxic potential of Paraopeba River water. Thus, the Allium cepa test system was applied, along with physicochemical analyses, flow cytometry, and metal concentration, comparing the results between the rainy and dry seasons three years after the dam rupture. The tests were conducted on water samples

QbD-Based HPLC Method Development for Trace-Level Detection of Genotoxic 3-Methylbenzyl Chloride in Meclizine HCl Formulations.

A robust and sensitive reversed-phase HPLC method was developed and validated for the quantitative determination of 3-methyl benzyl chloride, a potential genotoxic process impurity, in Meclizine HCl formulations. The separation was achieved on a C18 column using an isocratic mobile phase consisting of a 0.025-M sodium 1-heptanesulfonate buffer (pH 4.0, adjusted with 0.1 N sulfuric acid) and acetonitrile (600:400, v/v). Detection was performed at 210 nm. A quality-by-design approach, specifically a Box-Behnken design, was employed to optimize key chromatographic parameters including flow rate,

Is genotoxicity a suitable biomarker for monitoring anabolic-androgenic steroids exposure in vivo? A systematic review and meta-analysis.

Steroids stand for a class of hormones (natural and synthetic) known to be helpful for a number of disorders. Despite the aforementioned beneficial effects of using these hormones, anabolic-androgenic steroids (AAS) are also widely abused in a non-therapeutic manner for muscle-building and strength-increasing properties that may lead to genotoxicity in different tissues. The present study aims to understand whether genotoxicity may be a suitable biomarker for AAS exposure in vivo in both experimental animal and human studies. All studies published in PubMed/Medline, Scopus, and Web of Science

Non-clinical safety evaluation of salvianolic acid A: acute, 4-week intravenous toxicities and genotoxicity evaluations.

BACKGROUND: Toxicological problem associated with herbal medicine is a significant public health problem. Hence, it is necessary to elaborate on the safety of herbal medicine. Salvianolic acid A (SAA) is a major active compound isolated from Danshen, a popular herbal drug and medicinal food plant in China. The aim of the present study was to explore the toxicological profile of SAA. METHODS: The acute toxicity studies were performed in mice and Beagle dogs with single administration with SAA. A 4-week subchronic toxicity was test in dogs. SAA was intravenously administered at doses of 20, 80

RIFM fragrance ingredient safety assessment, l-carvone, CAS Registry Number 6485-40-1.

l-Carvone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that l-carvone is not genotoxic and provided a No Expected Sensitization Induction Level (NESIL) of 2600 μg/cm2 for the skin sensitization endpoint. Data on l-carvone provided a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. The phototoxicity/photoallergenicity endpoint was completed based on data and ultraviolet/visible (UV/Vis)

Melatonin Loading Chitosan-Tripolyphosphate Nanoparticles: Application in Attenuating Etoposide-Induced Genotoxicity in HepG2 Cells.

Etoposide is one of the most effective chemotherapeutic agents used in the treatment of various types of cancers. However, as a Topoisomerase II inhibitor, during clinical use, several side effects may occur. In addition, in several in vivo and in vitro studies, etoposide has been shown to have a range of genotoxic effects including single and double strand breaks. Melatonin is an anti-aging and antioxidant hormone synthesized from the pineal gland. The genoprotective, antioxidant, and free radical scavenger properties of melatonin have been well explained in various studies. The aim of this s

The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection.

Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine infection. Immunocompetent mice were infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional or an inactive typhoid toxin. The p